The title compounds are related to the family of natural oligopeptide antiviral antitumor antibiotics which include netropsin (Julia, M., Preau-Joseph, N. C. R., Hebd-Seances, Acad. Sci., 1963, 257, 1115) and distamycin (Arcamone, F., Orezzi, P. G., Barbier, W., Nicolella, V., Penco, S., Gazz. Chim. Ital., 1967, 97, 1097). ##STR2##
These structures contain pyrrole moieties connected by peptide bonds and with side chains, at least one of which is positively charged, i.e. an amidine group, N-formyl or a group of the guanidyl type.
Of this group of natural oligopeptide antibiotics only distamycin has been used as a therapeutic agent under the name of Stallimycin Hydrochloride in the form of a 1% cream, ointment or paste (Martindale, The Extra Pharmacopoeia, Twenty-eighth Edition, p. 825,1982) in treatments of infections produced by herpes simplex, herpes zoster and vaccinia viruses. The external use limitation of distamycin is due to its high cytotoxicity and a low therapeutic index which in the case of herpes viruses is about 3.
Other pertinent compounds are the natural product CC-1065 (Reynolds, V. L., Molineux, T. J., Kaplan, D., Swenson, D. H., Hurley, L. H., Biochemistry, 1985, 24, 6228), and the synthetic agent ##STR3## FCE245517 (Arcamone, F. M., Animati, F., Barbieri, B., Configliacchi, E., D'Alessio, R., Geroni, C., Giulani, F. C., Lazzari, E., Menozzi, M., Mongetti, N., Penco, S., Verini, A., J. Med. Chem., 1989, 32, 774. ##STR4## Whereas CC-1065 itself is too toxic for clinical applications because of the delayed death syndrome three synthetic analogs produced by Upjohn are in clinical trials. Compound FCE 24517 is also undergoing clinical trials at this time.